TCP shortens the latency of onset of isoelectricity in hypoglycaemia and fails to protect striatal neurones and dentate gyrus granule cells from hypoglycaemic injury in rats.
Competitive N-methyl-D-aspartate (NMDA) receptor antagonists are known to protect neurones against hypoglycaemic damage. We tested N-[1-(2-thienyl)cyclohexyl]piperidine (TCP), a non-competitive NMDA antagonist, in a recovery model of hypoglycaemic coma in the rat. Administered concomitantly with insulin, TCP shortened the latency of onset of electrocerebral silence, and failed to prevent striatal and dentate gyrus hypoglycaemia-induced injury. This effect is probably related to an increase in glucose consumption of neurones: TCP enhances energy metabolism in several brain structures, which could facilitate, at low blood glucose levels, the onset of isoelectricity, and hamper a putative neuro-protective effect of the drug.
Torres
J H
JH
Laboratoire de Médecine Expérimentale, INSERM U 249, CNRS UPR 41, Institut de Biologie, Montpellier, France.
Rondouin
G
G
Kamenka
J M
JM
Chicheportiche
R
R
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D004569:Electroencephalography; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D013287:Illicit Drugs; D007328:Insulin; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013997:Time Factors
D013287:Illicit Drugs; D007328:Insulin; C012058:tenocyclidine; D010622:Phencyclidine